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DOUBLE-LUNG TRANSPLANTS WORK BETTER THAN SINGLE FOR LONG-TERM SURVIVAL

- Immune system matching and college education also important(Théàtre bleu, Palais des Congrès de Paris)

April 20, 2009- Having both lungs replaced instead of just one is the single most important feature determining who lives longest after having a lung transplant, more than doubling an organ recipient’s chances of extending their life by over a decade, a study by a team of transplant surgeons at Johns Hopkins shows.

The finding is potentially controversial, researchers say, because there is already a shortage of organ donors, and more widespread use of bilateral lung transplants could nearly halve the potential number of beneficiaries. Though more than 1,400 lung transplants occurred in the United States in 2008, another 2,000 Americans remain on lung waiting lists, while 80 more are waiting for both a heart and lung.

“Our results suggest that double-lung transplants have a long-term advantage, and surgeons should consider bilateral lung transplants whenever possible,” says study senior investigator and transplant surgeon Ashish Shah, M.D. But, he notes, “Not all lung recipients necessarily need a bilateral transplant. Many people with chronic obstructive pulmonary disease, including emphysema and different kinds of pulmonary fibrosis, can survive with just one lung being replaced, while other lung diseases, such as cystic fibrosis, usually require transplantation of both lungs. But double-lung transplants clearly perform better over time.

“What we’re really after here is to find as many factors as possible that support long-term survival, so that we maximize the gains in average lifespan for all our patients,” says Shah.

Among the team’s other key findings, to be presented April 22 in Paris at the 29th annual meeting of the International Society for Heart & Lung Transplantation, are that a perfect or near perfect match between the donor’s immune-activating protein antigens with a recipient’s and having a college education increases chances for long-term survival by 38 percent and 40 percent, respectively.

The study, believed to be the most widespread search ever conducted for factors that may extend the life of lung transplant recipients, are among the first to emerge from an analysis of 836 so-called long-term survivors of lung transplants, men and women who have lived at least a decade after transplant surgery between 1987 and 1997, an extended period for which detailed medical histories are now available.

Seventeen percent of all lung transplant recipients survive this long or longer with their new lungs, a figure that Shah, an associate professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute, says is “pretty good, but not good enough” and the result of advances made in the last two decades with immune-suppressing drugs that prevent the recipient’s body from rejecting the transplant.

“Until now, we knew how best to ensure that transplant recipients survive for the first few months after surgery, avoiding infection of the transplanted lung, and then staying healthy for the next two years to five years. But we never really knew what factors distinguished the long-term survivors from those who succumbed earlier, to either organ rejection or death,” says Shah, who has performed over 100 lung transplants in the past decade.

Lead study investigator Eric Weiss, M.D., says that a patient’s education, though key, is more likely a cover or surrogate, masking some other factor or combination of factors that are accounting for the increased longevity. Possible explanations, he says, are that better educated people may have better health insurance and access to care than those with less formal schooling, or that people with degrees are better at keeping their physician appointments on schedule, taking their medications as prescribed and sooner alerting their physicians to problems.

“Our results are a reminder to both patients and physicians that we still have a lot to learn about how best to prolong lung transplant survival, and that we need to be constantly evaluating our procedures to determine what is in the patient’s best, long-term interests,” says Weiss, a postdoctoral research fellow in cardiac surgery at Hopkins.

Indeed, he points out that a key advantage in double-lung transplants over single-lung transplants is that residual disease is not left behind in the spared lung. Moreover, when both lungs are replaced, the new lungs, which must breathe together as a pair, are already adapted to each other.

The vast majority of the lung transplants performed by Shah’s team at The Johns Hopkins Hospital involve the fully paired organs, including 15 of 17 in 2008, 20 of 22 in 2007 and 20 of 23 in 2006.

In the latest study, long-term survival for lung recipients was also upped when they had “highly compatible” immune systems with their donor, with at least five of six so-called human leukocyte antigens (or HLA) the same as the donors. HLA antigens are proteins that sit on the cell surface and act like a secret passcode among the body’s cells, triggering the body’s immune system to reject anything that’s not recognizable as its own. The better the match, Weiss says, the better are chances for immunosuppressive drugs to work over the long term at preventing organ rejection.

The study analysis involved a detailed review of the patient records for all single-lung and double-lung transplants performed in the United States and Canada from 1987 to 1997. The data came from the United Network for Organ Sharing (UNOS), a national network that allocates donated organs across the country.

Weiss says the team next plans to evaluate what aspects of education make the difference in long-term survival, with the goal of identifying independent factors that can influence better adherence to drug treatment plans or that could potentially be altered in people to extend the amount of time they can potentially live with their new organ.

Funding for the study was supplied in part by the U.S. Health Resources and Services Administration, the U.S. National Institutes of Health, and the Joyce Koons Family Fund for Cardiac Surgery Research.

In addition to Shah and Weiss, other Johns Hopkins researchers involved in this study were Jeremiah G. Allen, M.D.; Christian Merlo, M.D., M.P.H.; and John Conte, M.D.